Differential DNA methylation in blood as potential mediator of the association between ambient PM<sub>2.5</sub> and cerebrospinal fluid biomarkers of Alzheimer's disease among a cognitively normal population-based cohort.
Overview
- Ganagarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, 30322 GA USA
- Department of Psychiatry, University of California, Davis, Sacramento, 95816 CA USA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, 30322 GA USA
- Goizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta, 30322 GA USA
- Department of Neurology, Emory University School of Medicine, Atlanta, 30322 GA USA
- Division of Mental Health, Northern California VA, Sacramento, 95816 CA USA
- Department of Neurology, University of California, Davis, Sacramento, 95816 CA USA
- Alzheimer’s Disease Research Center, University of California, Davis, Sacramento, 95816 USA
Abstract
Fine particulate matter (PM2.5) is a known risk factor for Alzheimer’s disease (AD), with emerging evidence showing its effects detectable in the pre-clinical stage through cerebrospinal fluid (CSF) biomarkers of AD. While studies have linked PM2.5 exposure and AD to DNA methylation (DNAm) alterations, the role of DNAm as potential mediator in the association between PM2.5 and AD biomarkers in cognitively normal individuals remains largely unexplored, and formal mediation analyses addressing this question are scarce. Genome-wide DNAm profiles (Illumina EPIC BeadChips) in whole blood and CSF Aβ42 concentrations were assessed in 536 cognitively normal individuals from the Emory Healthy Brain Study (EHBS). Residential PM2.5 exposure for the year preceding participants’ blood collection was estimated. A multi-stage analytical pipeline, incorporating single-mediator analysis, high-dimensional mediation analysis, and causal mediation analysis, was applied. Nine CpG sites were identified as noteworthy mediators of the relationship between PM2.5 and decreased CSF Aβ42 concentrations. Causal mediation analysis confirmed significant natural indirect effects (NIE) for eight CpGs, with effect estimates ranging from −0.015–−0.029 per 1 ug/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Codes for statistical analysis can be shared upon request.
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Data
Datasets cited
- geo:GSE111165, at NCBI GEO; found in the text, “Secondary analyses”
Data availability
Requests for data access should be submitted through the Goizueta Alzheimer’s Disease Research Center at Emory University via the following link: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 2, 28 September 2026
- Publisher: n/a → Springer Nature
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 2 keywords, 16 MeSH terms, 3 funders, 94 references.
Cite
This paper
Ma, T., Liu, J., Liang, D., Ebelt, S., Steenland, K., Levey, A. I., Lah, J. J., Wingo, A. P., Wingo, T. S., & Hüls, A. (2026). Differential DNA methylation in blood as potential mediator of the association between ambient PM&
BibTeX
@article{ma2026different
author = {Ma, Tszshan and Liu, Jiaqi and Liang, Donghai and Ebelt, Stefanie and Steenland, Kyle and Levey, Allan I and Lah, James J and Wingo, Aliza P and Wingo, Thomas S and Hüls, Anke},
title = {{Differential DNA methylation in blood as potential mediator of the association between ambient PM\&
journal = {Molecular psychiatry},
year = {2026},
month = jun,
volume = {31},
number = {10},
pages = {5811--5822},
publisher = {Springer Nature},
issn = {1359-4184},
doi = {10.1038/
url = {https://
pmid = {42270761},
pmcid = {PMC13358818}
}
RIS
TY - JOUR
AU - Ma, Tszshan
AU - Liu, Jiaqi
AU - Liang, Donghai
AU - Ebelt, Stefanie
AU - Steenland, Kyle
AU - Levey, Allan I
AU - Lah, James J
AU - Wingo, Aliza P
AU - Wingo, Thomas S
AU - Hüls, Anke
TI - Differential DNA methylation in blood as potential mediator of the association between ambient PM&
T2 - Molecular psychiatry
J2 - Mol Psychiatry
PY - 2026
DA - 2026/
VL - 31
IS - 10
SP - 5811
EP - 5822
SN - 1359-4184
PB - Springer Nature
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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